Tumor-associated macrophages promote oral squamous cell carcinoma development

Oral squamous cell carcinoma (OSCC), the most common oral malignancy, is characterized by poor prognosis, risk factors of tobacco and alcohol, and epithelial-specific mutations. Within the tumor microenvironment (TME) of OSCC, tumor-associated macrophages (TAMs) are key immune cells recruited to the tumor site and can be polarized into different phenotypes with either pro-inflammatory or anti-inflammatory functions. Therefore, there is a significant need to understand the role of TAMs in the OSCC microenvironment and the interaction between TAMs and cancer cells that may impact OSCC's aggressiveness and therapy resistance. Our lab has established cell lines from mouse oral tumors generated by activation of epithelial-specific mutations in mouse oral epithelium using both genetic and carcinogenic systems. Using these models, we employed an orthotopic and immunocompetent approach to study the specific functions of TAMs on the OSCC TME with surrounding lymphoid organs and highly dense vascularity. After orthotopic implantation, these cell lines developed oral tumors with high levels of TAM infiltration. To determine the role of TAMs in oral tumor development we depleted macrophages systemically with an anti-mouse Colony Stimulating Factor-1 Receptor (CSF1R). Results showed a significantly decreased tumor growth in mice injected with anti-CSF1R compared to untreated mice. Immunohistochemistry confirmed the loss of TAMs from the tumors treated with anti-CSF1R. Ongoing studies focus on investigating how macrophages remodel the tumor immune microenvironment of OSCC and modulate the malignant properties of oral cancer cells. We envision that these studies will help develop prevention and therapeutic approaches by targeting the pro-tumorigenic activities of TAMs in OSCC.